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Open Forum Infect Dis. 2019 Mar 14;6(4):ofz137. doi: 10.1093/ofid/ofz137. eCollection 2019 Apr.
Clinical Development of Therapeutic Agents for Hospitalized Patients With Influenza: Challenges and Innovations.
King JC1, Beigel JH2, Ison MG3, Rothman RE4, Uyeki TM5, Walker RE1, Neaton JD6, Tegeris JS1, Zhou JA1, Armstrong KL1, Carter W7, Miele PS7, Willis MS1, Dugas AF8, Tracy LA7, Vock DM6, Bright RA1.
Author information
Abstract
Background:
Since 1999, the US Food and Drug Administration approved neuraminidase and endonuclease inhibitors to treat uncomplicated outpatient influenza but not severe hospitalized influenza. After the 2009 pandemic, several influenza hospital-based clinical therapeutic trials were unsuccessful, possibly due to certain study factors. Therefore, in 2014, the US Health and Human Services agencies formed a Working Group (WG) to address related clinical challenges.
Methods:
Starting in 2014, the WG obtained retrospective data from failed hospital-based influenza therapeutic trials and nontherapeutic hospital-based influenza studies. These data allowed the WG to identify factors that might improve hospital-based therapeutic trials. These included primary clinical endpoints, increased clinical site enrollment, and appropriate baseline enrollment criteria.
Results:
During 2018, the WG received retrospective data from a National Institutes of Health hospital-based influenza therapeutic trial that demonstrated time to resolution of respiratory status, which was not a satisfactory primary endpoint. The WG statisticians examined these data and believed that ordinal outcomes might be a more powerful primary endpoint. Johns Hopkins' researchers provided WG data from an emergency-department (ED) triage study to identify patients with confirmed influenza using molecular testing. During the 2013-2014 influenza season, 4 EDs identified 1074 influenza-patients, which suggested that triage testing should increase enrollment by hospital-based clinical trial sites. In 2017, the WG received data from Northwestern Memorial Hospital researchers regarding 703 influenza inpatients over 5 seasons. The WG applied National Early Warning Score (NEWS) at patient baseline to identify appropriate criteria to enroll patients into hospital-based therapeutic trials.
Conclusions:
Data received by the WG indicated that hospital-based influenza therapeutic trials could use ordinal outcome analyses, ED triage to identify influenza patients, and NEWS for enrollment criteria.
KEYWORDS:
antivirals; clinical site recruitment; enrollment criteria; influenza; therapeutic trial endpoints
PMID: 31037242 PMCID: PMC6479095 DOI: 10.1093/ofid/ofz137
Free PMC Article
Clinical Development of Therapeutic Agents for Hospitalized Patients With Influenza: Challenges and Innovations.
King JC1, Beigel JH2, Ison MG3, Rothman RE4, Uyeki TM5, Walker RE1, Neaton JD6, Tegeris JS1, Zhou JA1, Armstrong KL1, Carter W7, Miele PS7, Willis MS1, Dugas AF8, Tracy LA7, Vock DM6, Bright RA1.
Author information
Abstract
Background:
Since 1999, the US Food and Drug Administration approved neuraminidase and endonuclease inhibitors to treat uncomplicated outpatient influenza but not severe hospitalized influenza. After the 2009 pandemic, several influenza hospital-based clinical therapeutic trials were unsuccessful, possibly due to certain study factors. Therefore, in 2014, the US Health and Human Services agencies formed a Working Group (WG) to address related clinical challenges.
Methods:
Starting in 2014, the WG obtained retrospective data from failed hospital-based influenza therapeutic trials and nontherapeutic hospital-based influenza studies. These data allowed the WG to identify factors that might improve hospital-based therapeutic trials. These included primary clinical endpoints, increased clinical site enrollment, and appropriate baseline enrollment criteria.
Results:
During 2018, the WG received retrospective data from a National Institutes of Health hospital-based influenza therapeutic trial that demonstrated time to resolution of respiratory status, which was not a satisfactory primary endpoint. The WG statisticians examined these data and believed that ordinal outcomes might be a more powerful primary endpoint. Johns Hopkins' researchers provided WG data from an emergency-department (ED) triage study to identify patients with confirmed influenza using molecular testing. During the 2013-2014 influenza season, 4 EDs identified 1074 influenza-patients, which suggested that triage testing should increase enrollment by hospital-based clinical trial sites. In 2017, the WG received data from Northwestern Memorial Hospital researchers regarding 703 influenza inpatients over 5 seasons. The WG applied National Early Warning Score (NEWS) at patient baseline to identify appropriate criteria to enroll patients into hospital-based therapeutic trials.
Conclusions:
Data received by the WG indicated that hospital-based influenza therapeutic trials could use ordinal outcome analyses, ED triage to identify influenza patients, and NEWS for enrollment criteria.
KEYWORDS:
antivirals; clinical site recruitment; enrollment criteria; influenza; therapeutic trial endpoints
PMID: 31037242 PMCID: PMC6479095 DOI: 10.1093/ofid/ofz137
Free PMC Article